Richard Silverman, MD
About
Research
Publications
2025
Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases
Johnson E, Nowar R, Viola K, Huang W, Zhou S, Bicca M, Zhu W, Kranz D, Klein W, Silverman R. Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2402117122. PMID: 40030015, PMCID: PMC11912461, DOI: 10.1073/pnas.2402117122.Peer-Reviewed Original ResearchConceptsProtein aggregationNeurodegenerative diseasesMechanisms of protein aggregationAmyloid-beta oligomersAlzheimer's disease neurodegenerationEndolysosomal traffickingBeta oligomersOligomer accumulationTreatment of neurodegenerative diseasesTDP-43Disease neurodegenerationPeptide aggregationLysosome-dependentCathepsin LProteinHippocampal neuronsPathological accumulationQuantitative assayTraffickingCellular mechanismsCathepsin BBlock neurodegenerationImmunofluorescence imagingPathogenic mechanismsNeurodegenerationCrosstalk Between nNOS/NO and COX-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression
Patel A, Tong S, Roosan M, Syed B, Awasthi A, Silverman R, Yang S. Crosstalk Between nNOS/NO and COX-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression. Cancers 2025, 17: 477. PMID: 39941844, PMCID: PMC11816268, DOI: 10.3390/cancers17030477.Peer-Reviewed Original ResearchNeuronal nitric oxide synthaseIFN-gPro-tumorigenic activityCOX-2Human melanoma xenograft mouse modelMelanoma progressionMelanoma cellsFlow cytometryInduction of neuronal nitric oxide synthaseNeuronal nitric oxide synthase blockadeIn vivo antitumor efficacyMelanoma xenograft mouse modelMelanoma tumor microenvironmentLevels of PGE<sub>2</sub>PD-L1 expressionAnticancer immune responseMelanoma tumor growth in vivoCOX-2 expression levelsAnalysis of patientsInduction of COX-2Increased intracellular NO levelsSTAT3 inhibitor NapabucasinNitric oxideInhibited COX-2 expressionXenograft mouse modelProtection against Amyloid‑β Aggregation and Ferroptosis/Oxytosis Toxicity by Arylpyrazolones: Alzheimer’s Disease Therapeutics
Soares P, Rahaman M, Maher P, Silverman R. Protection against Amyloid‑β Aggregation and Ferroptosis/Oxytosis Toxicity by Arylpyrazolones: Alzheimer’s Disease Therapeutics. ACS Medicinal Chemistry Letters 2025, 16: 294-300. PMID: 39967645, PMCID: PMC11831554, DOI: 10.1021/acsmedchemlett.4c00530.Peer-Reviewed Original ResearchSynthesis of Oxabicyclo[3.2.1]octan-3-ol Scaffold via Burgess Reagent Mediated Cyclodehydration of δ‑Diols under Acidic Conditions
Elmansy M, dos Remedios J, Silverman R. Synthesis of Oxabicyclo[3.2.1]octan-3-ol Scaffold via Burgess Reagent Mediated Cyclodehydration of δ‑Diols under Acidic Conditions. Organic Letters 2025, 27: 640-644. PMID: 39761354, PMCID: PMC11901898, DOI: 10.1021/acs.orglett.4c04473.Peer-Reviewed Original Research
2024
Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction
Wirt J, Ferreira L, Jesus C, Woodward T, Oliva I, Xu Z, Crystal J, Pepin R, Silverman R, Hohmann A. Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 122: e2318833121. PMID: 39793055, PMCID: PMC11725897, DOI: 10.1073/pnas.2318833121.Peer-Reviewed Original ResearchConceptsComplete Freund's adjuvantInflammatory painMechanical hypersensitivityAntinociceptive efficacyGlutamate levelsInjection of complete Freund's adjuvantConditioned place preference assayPaclitaxel-induced mechanical hypersensitivitySpinal site of actionSide effectsEnhancement of GABAergic transmissionChemotherapeutic agent paclitaxelPaclitaxel-induced increaseCompared to morphineLumbar spinal cordIncreased endogenous GABA levelsReduced glutamate levelsNeuropathic nociceptionSite of actionGABAergic transmissionAnalgesic strategiesPathological painGABAergic inhibitionSpinal sitesAbuse liabilityCorrection to “Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase”
Devitt A, Vargas A, Zhu W, Des Soye B, Butun F, Alt T, Kaley N, Ferreira G, Moran G, Kelleher N, Liu D, Silverman R. Correction to “Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase”. ACS Chemical Biology 2024, 19: 1850-1850. PMID: 39023367, DOI: 10.1021/acschembio.4c00478.Peer-Reviewed Original ResearchSynthesis of (2R,4S)‑4-Amino-5-hydroxybicyclo[3.1.1]heptane-2-carboxylic Acid via an Asymmetric Intramolecular Mannich Reaction
Dukes A, Weerawarna P, Devitt A, Silverman R. Synthesis of (2R,4S)‑4-Amino-5-hydroxybicyclo[3.1.1]heptane-2-carboxylic Acid via an Asymmetric Intramolecular Mannich Reaction. The Journal Of Organic Chemistry 2024, 89: 9110-9117. PMID: 38857432, PMCID: PMC11418922, DOI: 10.1021/acs.joc.4c00781.Peer-Reviewed Original ResearchDesign, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase
Devitt A, Vargas A, Zhu W, Soye B, Butun F, Alt T, Kaley N, Ferreira G, Moran G, Kelleher N, Liu D, Silverman R. Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase. ACS Chemical Biology 2024, 19: 1066-1081. PMID: 38630468, PMCID: PMC11274680, DOI: 10.1021/acschembio.4c00022.Peer-Reviewed Original ResearchConceptsActive siteX-ray crystallographyIntact protein mass spectrometryHuman ornithine aminotransferaseNucleophilic additionRing scaffoldMass spectrometryIntermediate speciesProtein mass spectrometryIncreased selectivityTransient state kinetic studiesX-rayMechanistic studiesAdductsSolvent accessibilityKinetic studiesHepatocellular carcinomaProgression of hepatocellular carcinomaMechanism of inactivationStructural evidencePrevalence of hepatocellular carcinomaTreatment of hepatocellular carcinomaCyclohexeneCyclopenteneCrystallographyCrystallographic and Computational Insights into Isoform-Selective Dynamics in Nitric Oxide Synthase
Li H, Hardy C, Reidl C, Jing Q, Xue F, Cinelli M, Silverman R, Poulos T. Crystallographic and Computational Insights into Isoform-Selective Dynamics in Nitric Oxide Synthase. Biochemistry 2024, 63: 788-796. PMID: 38417024, PMCID: PMC10956423, DOI: 10.1021/acs.biochem.3c00601.Peer-Reviewed Original ResearchConceptsHydrogen bondsHeme propionatesDimer interfaceInhibitor bindingCombination of crystallographyInhibitor binding siteDevelopment of isoform-selective inhibitorsIsoform-selective inhibitorsStructural basisComputational insightsStructural changesInhibitor moleculesChanges conformationBinding sitesConformational changesBondsSite inhibitorsPterin cofactorBindingHydrogenSynthaseDimerStructural differencesTyrosineInhibitors
2023
Target Identification of a Class of Pyrazolone Protein Aggregation Inhibitor Therapeutics for Amyotrophic Lateral Sclerosis
Weerawarna P, Schiefer I, Soares P, Fox S, Morimoto R, Melani R, Kelleher N, Luan C, Silverman R. Target Identification of a Class of Pyrazolone Protein Aggregation Inhibitor Therapeutics for Amyotrophic Lateral Sclerosis. ACS Central Science 2023, 10: 87-103. PMID: 38292603, PMCID: PMC10823514, DOI: 10.1021/acscentsci.3c00213.Peer-Reviewed Original Research